A 9-year-old boy with fever, rash

A 9-year-old boy was seen at an outside emergency room for evaluation of fever and rash of nine days duration. He had been seen by his primary physician after one day of illness and was diagnosed with a “viral syndrome.” The rash was first noted on his arms and legs but eventually involved his entire body. He also complained of headache and abdominal pain. He had one episode of emesis and several loose stools. At the emergency room, he was given a shot of ceftriaxone and transferred to Carolinas Medical Center for further evaluation and management.

He lived in rural North Carolina and frequently played in the woods near his house, though he had no specific history of a tick bite. He has no other significant past medical history.

Examination revealed an ill-appearing boy who was irritable but oriented. His temperature was 103.5º F. He had a petechial rash over his entire body, which included his palms and soles (figures 1-3). His lips were dry and cracked, and he had palatal petechiae. The remainder of his exam was unremarkable.

Laboratory tests at admission included hemoglobin of 10.2, platelet count of 450,000, BUN of 23, AST of 215, sodium of 134. Cerebrospinal fluid glucose was 43, protein 97, WBC 38 with lymphocyte predominance.

On admission, treatment with ceftriaxone and doxycycline was begun. Soon thereafter, he had significant neurologic deterioration with increasing agitation and confusion. New findings on reexamination included left-sided weakness and brisk reflexes with clonus. He also developed increasing respiratory distress and required intubation with mechanical ventilation.

What’s your diagnosis?

1. Meningococcemia
2. Rocky Mountain spotted fever
3. Ehrlichiosis
4. Hemolytic uremic syndrome

Case Discussion

The answer is Rocky Mountain spotted fever (RMSF). This child’s blood and spinal fluid cultures were negative, and he tested positive by latex agglutination for RMSF.

The severe deterioration, which occurred on day nine of his illness, is unfortunately typical for untreated RMSF, a vasculitic infection caused by the small Gram-negative bacterium Rickettsia rickettsii. It is the most common fatal tick-borne illness in the United States, with cases reported throughout the continental United States.

Despite its name, RMSF is most common in the southeastern United States in a swath stretching from North Carolina and Virginia to Oklahoma.

The primary vectors are the dog tick (Dermacentor variabilis) in the eastern United States and the wood tick (Dermacentor andersonii) in the west.

The “classic triad” of RMSF consists of fever, rash and history of a tick bite. Diagnosis is made more difficult by the fact that less than one-quarter of the patients will have all three elements of the triad at the time of presentation. Virtually all patients have fever, but one-third of patients will not recall a tick bite.

The typical rash is petechial, beginning on the extremities and spreading centrally. Involvement of the palms and soles is common. However, wide variation in the onset and nature of the rash is seen. The rash often does not appear until day four or five of illness, and it may initially appear as a nonspecific macular exanthem that blanches with pressure.

RMSF is a multi-system disease, and findings are not limited to the skin. Headache, myalgia, nausea, vomiting, diarrhea and respiratory difficulty are all common complaints. Frequent physical findings include conjunctivitis, lymphadenopathy, and hepatosplenomegaly. Central nervous system manifestations, including severe headache, photophobia, altered mental status and seizures, are common. About one-third of patients develop aseptic meningoencephalitis, documented by sterile cerebrospinal fluid with pleocytosis and high protein level. Magnetic resonance imaging has been reported to show numerous punctuate areas of increased signal in the perivascular spaces on T2 weighted images, giving a picture of “Rocky Mountain Spotted Encephalitis.” Our patient had this pattern on MRI (figure 4). A significant percentage of patients have residual neurological deficits at the time of hospital discharge.

Diagnosis must be made clinically. Laboratory abnormalities, including thrombocytopenia, hyponatremia and elevated hepatic transaminases can support the diagnosis but are nonspecific and are not always present. Serologic tests can confirm the diagnosis, but there are many false negatives especially early in the illness. This is a common problem with many diseases diagnosed by serology; by the time the convalescent serum turns positive it is too late. Thus, the clinician must consider the possibility of RMSF in children with fever and no source, especially in highly endemic areas during the tick season of April through October.

Delay in diagnosis and treatment is strongly associated with complications and death. The disease may become fulminant, generally after day five, with coagulopathy, shock, coma and respiratory failure. The vasculitis may become severe enough to cause necrosis of the skin or distal tips of extremities (figure 5). Treatment by day five generally prevents these serious complications.

Doxycycline is the treatment of choice, and appears to be superior to chloramphenicol. Pediatricians should not fear doxycycline, which has lower calcium binding than other tetracyclines and is unlikely to stain the teeth. Given the difficulty with laboratory diagnosis and the severe consequences of delay, the empiric use of doxycycline of children with suspected RMSF is clearly justified.

Infection with Neisseria meningitidis is a much-feared disease that may present with fever, petechiae, purpura and meningitis (Figure 6). Thus, it may closely resemble RMSF. The more sub-acute course in this patient made meningococcemia less likely but it was enough of a concern to warrant the continued use of ceftriaxone while cultures were pending. Negative blood and CSF cultures drawn before antibiotics ruled out this diagnosis.

Ehrlichiosis is another important tick borne infection, caused by rickettsial-like organisms. There are two forms in the United States: human monocytic ehrlichiosis caused by Ehrlichia chaffeensis and human granulocytic ehrlichiosis (Anaplasmosis) caused by Anaplasma phagocytophilum. Both organisms are transmitted by Ixodes ticks. These infections generally result in milder, nonspecific illnesses characterized by fever, headache, malaise and myalgia. They are much less likely than RMSF to have a rash (sometimes referred to as Rocky Mountain Spotless Fever), and fulminant disease is uncommon. Diagnosis is usually by serology and treatment is with tetracyclines.

Hemolytic uremic syndrome (HUS) most commonly occurs after diarrhea due to Shiga toxin-producing E. coli. This illness presents with microangiopathic hemolytic anemia, acute renal failure and thrombocytopenia. The thrombocytopenia is usually not associated with a petechial or purpuric rash. Most patients are not acutely febrile, though some children with pneumococcal disease can develop HUS. Neurological complications are common, but usually consist of altered mental status and seizures rather than aseptic meningoencephalitis. Antibiotics are not helpful and may be harmful in patients with Shiga toxin-associated HUS. Treatment is supportive.

Columnist comments

I would like to thank Dave Rupar for contributing this outstanding case of Rocky Mountain Spotted Fever. As the summer brings on more tick activity, we all need to be vigilant to the early findings, and treat early in suspicious cases pending confirmation.

I understand how these diseases occur, but I’m still amazed that such small vectors can inject an organism that can bring down a person thousands of times larger; sort of like the mosquitoes spreading yellow fever that destroyed entire communities throughout the South in the 19th century, or the virus in H. G. Wells’s War of the Worlds that destroyed the alien invaders from Mars (I know it was just a story, but it could happen. Well, it could!).

On a more serious note, my friend, Dr. Mark Burnett (pictured with Russell Steele and me at the 2008 Uniformed Services Pediatric Seminar in Hawaii) is a pediatric infectious diseases specialist with the Army Medical Corps, stationed with a Calvary unit in Afghanistan, and is doing a lot of humanitarian work with the local physicians in a very austere and difficult environment.

He is taking on the task of trying to acquire some relatively recent medical textbooks to supply the clinics there. Perhaps you have a book or two that you have recently replaced with a new edition, and would not miss the older one(s). Mark indicates that the situation among the Afghan physicians is so Spartan that anything would be greatly appreciated.

If you are able to help, the APO address below can be used with the assurance that what you send will reach Dr. Burnett for appropriate distribution. The cost would be the same as mailing a box anywhere in the United States. It would be shipped and delivered as any other “care package.”

Medical Officer
PRT Kunar (Asadabad)
APO AE 09354

I’m sending my old Harriet Lane Handbook and a few textbooks. Please help if you can.

Thanks and keep in touch,

– James H. Brien

David G. Rupar, MD, is currently Director of the Division of Pediatric Infectious Diseases at the Levine Children’s Hospital in Charlotte, NC. He is a 1979 graduate of Georgetown University School of Medicine. His pediatric residency was in Dayton, OH at the USAF Medical Center Wright-Patterson/Wright State University, and he trained in Infectious Diseases at St. Christopher’s Hospital for Children in Philadelphia.

James H. Brien, DO, is Head of the Pediatric Infectious Diseases Section at The Children’s Hospital at Scott and White and is the Associate Professor of Pediatrics at Texas A&M University, College of Medicine, Temple, Texas. E-mail: jhbrien@aol.com

What’s Your Diagnosis? is a monthly case study featured in Infectious Diseases in Children, with treatment information and discussion to follow.